Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues
Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues
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DOI：
10.1038/ejhg.2013.210
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发表时间：
2014-05-01
影响因子：
5.2
通讯作者：
Al-Saif, Amr
中科院分区：
文献类型：
--
作者：
Bohlega, Saeed;Al-Ajlan, Huda;Al-Saif, Amr
Fibulin-1是一种细胞外基质蛋白，在各种组织的弹性纤维和基底膜的结构中具有重要作用。通过纯合性定位和外显子组测序，我们发现了一个错义突变，p。（Cys 397 Phe），在fibulin-1的3例患者从一个血缘家庭提出了一种新的综合征并指，隐睾，延迟运动里程碑，精神发育迟滞和脑萎缩的迹象。所发现的突变与表型分离，在374个群体匹配的等位基因中未发现。受影响的半胱氨酸在脊椎动物中高度保守，预计其突变会消除定义fibulin-1三级结构的二硫键。我们的研究结果强调了fibulin-1在中枢神经系统和各种结缔组织发育中的关键作用。2013年10月2日在线发布
Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues. published online 2 October 2013